4-Toluenesulfonyl chloride → (R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

HRID 1909699Notes

Reaction equation

HRID 1909699 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][OH:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 688279N-(tert-Butoxycarbonyl)-D-prolinol

Product 1

HCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of (R)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.43 g, 52 mmol, 1 eq.) in pyridine (50 ml) was added p-toluenesulfonyl chloride (10.5 g, 55 mmol, 1.06 eq.) in one portion at 0° C. The resulting mixture was stirred at rt overnight. And then poured into ice-water (250 ml). The mixture was extracted with EtOAc (50 ml×3). The combined EtOAc layers was washed with water (50 ml) followed by 1N HCl (75 ml×4) and NaHCO3 aq. (75 ml), dried over MgSO4. Evaporation of solvent under reduced pressure gave the desired product as colorless oil (18 g, 100% yield); 1H NMR (400 MHz, CDCl3) δ 1.28˜1.39 (m, 9H), 1.60˜1.90 (m, 4H), 2.42 (s, 3H), 3.20 (m, 2H), 3.83 (m, 1H), 4.0 (m, 2H), 7.48 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz, 2H);

Workup

  1. extractionThe mixture was extracted with EtOAc (50 ml×3)
  2. washThe combined EtOAc layers was washed with water (50 ml)
  3. dry with materialdried over MgSO4
  4. customEvaporation of solvent under reduced pressure

Sources & evidence

ORD record
ord-48321b209deb41e69131b35e557878f6
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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